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Kriteriem úãinné léãby folikulárního lymfomu je tedy dnes dosaÏení nejen klinické ale i robert Aebi suisse proti stárnutí remise. Tabulka 6 uvádí studie s fludarabinov˘mi reÏimy a hodnocením molekulárních odpovûdí. Kombinace fludarabinov˘ch reÏimÛ s rituximabem dosahují rovnûÏ v˘borné v˘sledky a jeví se jako velmi perspektivní. Fludarabin má ale také svÛj toxick˘ potenciál. Tento fakt je obávan˘ a limituje do jisté míry podání fludarabinov˘ch reÏimu v primární léãbû.

V souãasné dobû se objevují léãebná robert Aebi suisse proti stárnutí sekvenãního podání fludarabinov˘ch cyklÛ s jinou chemoterapií. Cílem je vyuÏít plnû cytostatick˘ potenciál fludarabinu za souãasného sníÏení toxick˘ch projevÛ.

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Literatura 1. N Engl J Med.

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J Clin Oncol. Cancer statistics. CA: A cancer Journal for Clinicians.

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Montgomery JA and Hewson K. Nucleosides of 2-fluoroadenine.

J Med Chem ; Cancer Chemother Pharmacol ; Leukemia ; 1: Sem Oncol ; 17 suppl 8 : Pharmacokinetic study of fludarabine phosphate NSC Metabolism and chemotherapeutic activity of 9-β-D-arabinofuranosylfluoroadenine against murine leukemia L and evidence for its phosphorylation by deoxycitidine kinase. Cancer Res ; Comparison of the toxicity and metabolism of 9-β-D-arabinofuranosylfluoroadenine and 9-β-Darabino-furanosyladenine in human lymphoblastoid cells.

Metabolism and action of fludarabine phosphate. Sem Oncol ; 17 suppl 7 : Blood ; Comparison of the actions of 9β-D-arabinofuranosylfluoroadenine and 9-β-D-arabinofuranosyl-adenine on target enzymes from mouse tumor cells.

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Termination of DNA synthesis by 9-β-D-arabinofuranosylfluoroadenine: a mechanism of cytotoxicity. J Biol Chem ; A mechanism of DNA synthesis inhibition. Lindahl T and Barnes DE. Mammalian DNA ligases. Ann Rev Biochem ; In: Magrath I.

Arnold London; Biochem Pharmacol ; Differential induction of apoptosis by fludarabine monophosphate in leukemic B and normal T cells in chronic lymphocytic leukemia. Drug-induced apoptosis in chronic lymphocytic leukemia.

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Leukemia ; Sampath D, Plunkett W. The role of c-Jun kinase in the apoptoptic response to nucleoside analogue-induced DNA damage. Proposed mechanism of therapeutic selectivity for 9-β-D-arabinofuranosylfluoro-adenine against murine leukemia based upon lower capacities for transport and phosphorylation in proliferative intestinal epithelium compared to tumor cells.

Specificity of systems mediating transport of adenosine, 9-β-D-arabinofuranosylfluoroadenine, and other purine nucleoside anlogues in L cells. Modulation of arabinosylcytosine metabolism by arabinosylfluoradenine in lymphocytes from patients with chronic lymphocytic leukemia: implications for combination therapy.

Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase-independent mechanism involving the generation of reactive oxygen species.

Biologic response of B lymphoma cells to anti- CD 20 monoclonal antibody rituximab in vitro: CD55 and CD95 regulate complement-mediated cell lysis.

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Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity pf either drug alone. British J Haematol ; Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the Group protocol mechanism of the National Cancer Institute: five-year follow-up report.

J Clin Oncol ; Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone CAP for treatment of advanced-stage chronic lymphocytic leukaemia. Lancet ; Ann of Oncol ; Semin in Oncol ; Fludarabine containing-regimens may adversely affaect peripheral blood stem cell collection in low-grade Non-Hodgkin lymphoma patients.

Leukemia and Lymphoma ; Br J Haematol ; Blood ; 92 suppl 1 : a abstr Clinical experience with fludarabine and its immunosupressive effects in pretreated chronic lymphocytic leukemias and low-grade lymphomas. Severe immunodeficiency in patients treated with fludarabine monophosphate. Eur J Haematol ; Rituximab in combination with CHOP or fludarabine in low-grade lymphoma.

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Sem Oncol ; 29 suppl 1 :